In parallel with a recent rise in an aging population, there has been a rapid increase in patients suffering from degenerative brain nervous system diseases. The degenerative brain nervous system diseases may occur due to an aging-induced structural degeneration of brain nerve cells; a secondary symptom caused by adult diseases such as a circulatory disorder, etc.; or physical, mechanical factors such as traffic accidents, industrial accidents, carbon monoxide poisoning, etc., wherein Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, stroke and the like are known as related diseases thereof.
Meanwhile, a C-Jun N-terminal kinase (JNK), which is classified as a serine-threonine kinase, is also called a stress activated protein kinase (SAPK), which is one of the three subtypes of a mitogen activated protein kinase. The JNK is activated in reaction with various stimuli such as cytokine, mitogen, osmotic stress, ultraviolet irradiation, etc., wherein such activated JNK is known to stimulate the phosphorylation of numerous transcription factors including C-Jun of AP-1 as well as the phosphorylation of intracellular proteins such as Bcl2, p53, etc., which are associated with apoptosis. Also, JNK genes form different protein isoforms by means of a splicing process. Out of them, the distribution of JNK3 is concentrated in brain tissues, unlike about 10 other protein isoforms of the same kind, such that there have been various ongoing studies on a relation between the JNK3 and the degenerative brain nervous system diseases.
Particularly, the JNK3 carries out phosphorylation-activation of an amyloid precursor protein (APP), which is a main cause of Alzheimer's disease, such that the APP is located onto a cell membrane and its conversion into beta amyloid is stimulated. By doing so, the beta amyloid is formed, after which its resulting toxicity induces a neuronal cell death. In this case, it is reported that such activation of the JNK3 serves as a main factor. Also, it is seen that a mouse with Familial Alzheimer's diseases (FAD) showed a remarkable decrease in oligomeric beta amyloid and an increase in cognitive ability by means of the removal of the JNK3, and it is also found that a mouse with the JNK3 gene removed therefrom showed an acquisition of resistance to MPTP, a substance for causing Parkinson's disease; obtained an inhibitory effect on adverse reactions to a glutamate analogue, a neurotoxic substance; and the like.
Against such a background, there have been actively ongoing studies to find a JNK3 inhibitor as a novel substance for treating degenerative brain nervous system diseases (Korea Patent Publication No. 2001-0029352), but they have not been enough to produce satisfactory results yet.